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In most human tumors, the MAPK pathway is constitutively activated. Since p90RSK is downstream of MAPK, it is often hyperactive and capable of phosphorylating oncogenic substrates. We have previously shown that p90RSK phosphorylates MDM2 at S166, promoting p53 degradation in follicular thyroid carcinomas. Thus, the inhibition of p90RSK restores p53 expression, which in turn inhibits cell proliferation and promotes apoptosis. In the present study, we demonstrated that the p90RSK/MDM2/p53 pathway proved to be an excellent target in the therapy of tumors with MAPK hyperactivation. For this purpose, we selected p53wt melanoma, lung and medullary thyroid carcinoma cell lines with high activation of p90RSK. In these cell lines, we demonstrated that the p90RSK/MDM2/p53 pathway is implicated in the regulation of the cell cycle and apoptosis through p53-dependent transcriptional control of p21 and Bcl-2. Furthermore, with an immunohistochemical evaluation of primary melanomas and lung tumors, which exhibit highly activated p90RSK compared to corresponding normal tissue, we demonstrated that MDM2 stabilization was associated with p90RSK phosphorylation. The results indicate that p90RSK is able to control the proliferative rate and induction of apoptosis through the regulation of p53wt levels by stabilizing MDM2 in selected tumors with constitutively activated MAPKs, making p90RSK a new attractive target for anticancer therapy.

Background. Mexico has favorable agroclimatic conditions for the development of roselle, a crop with high world demand; however, it has low yields and domestic consumption relies more than 50% on imports. Objective. To describe the national production scenario and identifying the main challenges, as well as the strategic factors to increase potential of this crop in Mexico. Methodology. The research was conducted in three phases, using a descriptive, correlational and explanatory approach. Qualitative and quantitative information was collected through documentary review, in-depth interviews and panel of experts. The methods of analysis were descriptive statistics, correlational statistics and structural analysis MICMAC (Matrice d' Impacts Croisés Multiplication Appliqués à un Classement). Results. It was found that, in 2021, the per capita consumption was 137.58 g. During the period 2009-2019, the national production of roselle showed an increase of 56.2%, which is attributed to intensive growth. The high demand for labor in the harvest, the low prices of imported roselle, and the lack of government and scientific attention, impossibility of development of this crop. Implications. This study helps to understand the productive dynamics of roselle cultivation in Mexico as well as provides information and strategies to enhance its development. Conclusion. The key factors for the evolution of roselle production in the long term are differentiated public policies, competitiveness (substitutes, quality, prices) and social organization.

Investigations into traffic accidents that lead to the determination of their causes and consequences are useful to all interested parties, both in the public and private sectors. One of the phases of investigation is the capture of data enabling the complete reconstruction of the accident scene, which is usually the point at which a conflict arises between the slow process of information gathering and the need to restore normal traffic flow. To reduce to a minimum the time the traffic is halted, this paper follows a methodology to reconstruct traffic accidents and puts forward a series of procedures and tools that are applicable to both large and small scenarios. The methodology uses low-cost UAV-SfM in combination with UAS aerial image capture systems and inexpensive GNSS equipment costing less than €900. This paper describes numerous tests and assessments that were carried out on four potential work scenarios (E−1 and E−2 urban roads with several intersections; E−3, an urban crossing with medium slopes; and E−4, a complex road section with different land morphologies), assessing the impact of using simple or double strip flights and the number of GCPs, their spacing distance and different distribution patterns. From the different configurations tested, the best results were achieved in those offset-type distributions where the GCPs were placed on both sides of the working area and at each end, with a spacing between 100 and 50 m and using double strip flights. Our conclusion is that the application of this protocol would be highly efficient and economical in the reconstruction of traffic accidents, provide simplicity in implementation, speed of capture and data processing, and provide reliable results quite economically and with a high degree of accuracy with RMSE values below 5 cm.

In most human tumors, the MAPK pathway is constitutively activated. Since p90RSK is downstream of MAPK, it is often hyperactive and capable of phosphorylating oncogenic substrates. We have previously shown that p90RSK phosphorylates MDM2 at S166, promoting p53 degradation in follicular thyroid carcinomas. Thus, the inhibition of p90RSK restores p53 expression, which in turn inhibits cell proliferation and promotes apoptosis. In the present study, we demonstrated that the p90RSK/MDM2/p53 pathway proved to be an excellent target in the therapy of tumors with MAPK hyperactivation. For this purpose, we selected p53wt melanoma, lung and medullary thyroid carcinoma cell lines with high activation of p90RSK. In these cell lines, we demonstrated that the p90RSK/MDM2/p53 pathway is implicated in the regulation of the cell cycle and apoptosis through p53-dependent transcriptional control of p21 and Bcl-2. Furthermore, with an immunohistochemical evaluation of primary melanomas and lung tumors, which exhibit highly activated p90RSK compared to corresponding normal tissue, we demonstrated that MDM2 stabilization was associated with p90RSK phosphorylation. The results indicate that p90RSK is able to control the proliferative rate and induction of apoptosis through the regulation of p53wt levels by stabilizing MDM2 in selected tumors with constitutively activated MAPKs, making p90RSK a new attractive target for anticancer therapy. [ABSTRACT FROM AUTHOR]

SciELO (Scientific Electronic Library Online) es un modelo para la publicación de revistas científicas en Internet. Su objetivo principal es aumentar la difusión y visibilidad de la ciencia generada en Latinoamérica, el Caribe, España y Portugal. Es un modelo cooperativo descentralizado que agrupa colecciones nacionales y temáticas de revistas científicas que cumplen unos ciertos criterios de calidad. Su filosofía es facilitar el acceso universal y gratuito a las publicaciones científicas del ámbito latinoamericano y de este modo aumentar su visibilidad.

BackgroundPenile cancer (PC) is an extremely rare malignancy, and the patients at advanced stages have currently limited treatment options with disappointing results. Immune checkpoint inhibitors anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are currently changing the treatment of several tumors. Furthermore, the microsatellite instability (MSI) and the deficient mismatch repair system (dMMR) proteins represent predictive biomarkers for response to immune checkpoint therapy. Until present, few data have been reported related to PD-L1 expression and MSI in PC. The main aim of our study was the evaluation of PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) in immune cells and the analysis of dMMR/MSI status in a large series of PCs.MethodsA series of 72 PC, including 65 usual squamous cell carcinoma (USCC), 1 verrucous, 4 basaloid, 1 warty, and 1 mixed (warty-basaloid), was collected. Immunohistochemistry (IHC) was performed to assess PD-L1 expression using two different anti-PD-L1 antibodies (clone SP263 and SP142 Ventana) and MMR proteins expression using anti-MLH1, anti-PMS2, anti-MSH2, and anti-MSH6 antibodies. PCR analysis was performed for the detection of MSI status.ResultsOf the 72 PC cases analyzed by IHC, 45 (62.5%) cases were TC positive and 57 (79%) cases were combined positive score (CPS) using PDL1 SP263. In our cohort, TILs were present in 62 out of 72 cases (86.1%), 47 (75.8%) out of 62 cases showed positivity to PDL1 clone SP142. In our series, 59 cases (82%) had pMMR, 12 cases (16.7%) had lo-paMMR, and only 1 case (1.3%) had MMR. PCR results showed that only one case lo-paMMR was MSI-H, and the case dMMR by IHC not confirmed MSI status.ConclusionOur findings showed that PD-L1 expression and MSI status represent frequent biological events in this tumor suggesting a rationale for a new frontier in the treatment of patients with PC based on the immune checkpoint inhibitors.

Introduction and Aims: Current concept of coagulopathy in cirrhosis indicates that there is a rebalancing of hemostasis with plasma hypercoagulability. Bacterial infection can promotes releases of endothelial heparinoids. However, the effect of this condition on the thrombin generation is unknown. Our aim was to assess the effect of bacterial infection on thrombin generation in cirrhosis. Methods: 36 patients with cirrhosis and bacterial infection (infected group) were evaluated within 24 hours after start antibiotic and at least 5 days after infection resolution. 28 patients with decompensated cirrhosis and not infected (not infected group) were also enrolled and reevaluated, without any intervention between evaluation times. Primary endpoint was the effect of bacterial infection on thrombin generation (TG) parameter ETP with TM (ETP TM). TM is a protein C activator added to mimic in vivo conditions. ROTEM assays, INTEM and HEPTEM (heparinase modified), was performed to evaluate the endogenous heparinoids effect. Protein C (PC) and antithrombin (AT) assays were performed. All results were compared within each group between evaluation times. Results: ETP TM values in infected cirrhotics were significantly higher than after resolution of infection (from 1145.4 ± 360.7 nmol/L*min to 958.1 ± 254.8 nmol/L*min, p=0.005) - figure 1. A heparinoid effect was found only in infected cirrhotics, with CTINTEM duration significantly longer than CTHEPTEM (p=0.004). This effect disappeared after resolution of infection (p=0.75). PC and AT deficiencies were significantly more severe in infected patients (p

Simple Summary: In recent years, artificial intelligence has been used increasingly in medical practice. Technological progress has made it possible to digitize the slides of histological preparations, allowing the use of image processing and AI technologies in surgical pathology. This potentially reduces variability and improves the uniformity of some histological evaluations, such as cellularity assessment in bone marrow biopsies, which is traditionally performed visually by expert human observers, resulting in inter-observer and intra-observer variability. In this work, we developed an accurate AI-based tool for the automated quantification of cellularity in BMB histology and compared its performances with cellularity estimates from five expert hematopathologists. Our results showed the robustness of our model across users and two different scanners for digitized image generation. The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as.tiff images and.png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners. [ABSTRACT FROM AUTHOR]

Buddleja cordata cell suspension cultures could be used as a tool for investigating the capabilities of this species to tolerate heavy metals (HMs) and for assessing the effects of HMs on the accumulation of phenolic compounds in this species. It grows in a wide range of habitats in Mexico, including ultramafic soils, and mobilizes some HMs in the soil. The mobilization of these HMs has been associated with phenolic substances. In addition, this species is used in Mexican traditional medicine. In the present study, a B. cordata cell suspension culture was grown for 18 days in a culture medium enriched with Cu (0.03–0.25 mM), Fe (0.25–1.5 mM), Mn (0.5–3.0 mM), or Zn (0.5–2.0 mM) to determine the effects of these HMs on growth and HM accumulation. We also assessed the effects of the HMs on phenolic compound accumulation after 1 and 18 days of HM exposure. Cells were able to grow at almost all tested HM concentrations and accumulated significant amounts of each HM. The highest accumulation levels were as follows: 1160 mg Cu kg−1, 6845 mg Fe kg−1, 3770 mg Mn kg−1, and 6581 mg Zn kg−1. Phenolic compound accumulation was affected by the HM exposure time and corresponded to each HM and its concentration. Future research should analyze whole plants to determine the capabilities of Buddleja cordata to accumulate abnormally high amounts of HM and to evaluate the physiological impact of changes in the accumulation of phenolic compounds. [ABSTRACT FROM AUTHOR]

Introduction: Fine needle aspiration cytology (FNAC) combined with rapid on‐site evaluation (ROSE) and ancillary techniques is an accurate diagnostic tool for many pathologies. However, in some cases, it may not be sufficient for actionable diagnoses or molecular testing, especially for cases that require large immunohistochemical panels or cases in which histological features are mandatory for the diagnosis. Core needle biopsy (CNB), on the contrary, provides samples that are suitable for histological features and sufficient for all ancillary studies. However, CNB is often performed by radiologists or clinicians without the direct participation of cytopathologists, which can lead to missed or delayed diagnoses. This study reports on the experience of combining FNAC and CNB performed in one setting by cytopathologists. The aim was to evaluate the impact of CNB on FNAC and the diagnostic efficiency of the combined procedures. Materials and Methods: One hundred forty‐two FNAC and CNB procedures performed in the same setting over a period of 2 years were analysed. The FNAC diagnoses were compared and integrated with the subsequent CNB diagnoses. The impact of CNB was categorized as follows: non‐contributory, in cases of inadequate samples; confirmed, when the CNB and FNAC diagnoses were the same; improved, when the CNB diagnosis was consistent with the FNAC diagnosis and further specified the corresponding entity; allowed, when CNB produced a diagnosis that could not be reached by FNAC; changed, when the CNB changed the previous FNAC diagnosis. Results: CNB confirmed the FNAC diagnosis in 40.1% of cases (n = 57/142). CNB improved the FNAC diagnosis in 47.2% of cases (n = 67/142). CNB allowed a diagnosis that could not be performed on FNAC in 2.1% of cases (n = 3/142). CNB changed a previous FNAC diagnosis in 2.1% of cases (n = 3/142). CNB was non‐contributory in 8.4% of cases (n = 12/142). CNB produced a positive impact on the whole diagnostic procedure in 51.4% of total cases (n = 73/142). The combined FNAC and CNB resulted in actionable diagnoses in 91.5% of all cases (n = 130/142). A complete molecular assessment was successfully performed in 14.7% of cases (n = 21/142) utilizing either FNAC or CNB material. Conclusions: The combined use of FNAC and CNB in one setting improves the diagnostic accuracy of both procedures. This approach exploits the advantages of each procedure, enhancing the accuracy of the final diagnosis. [ABSTRACT FROM AUTHOR]

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.

Bladder cancer has a high incidence and is marked by high morbidity and mortality. Early diagnosis is still challenging. The objective of this study was to create a metabolomics-based profile of bladder cancer in order to provide a novel approach for disease screening and stratification. Moreover, the study characterized the metabolic changes associated with the disease. Serum metabolomic profiles were obtained from 149 bladder cancer patients and 81 healthy controls. Different ensemble machine learning models were built in order to: (1) differentiate cancer patients from controls; (2) stratify cancer patients according to grading; (3) stratify patients according to cancer muscle invasiveness. Ensemble machine learning models were able to discriminate well between cancer patients and controls, between high grade (G3) and low grade (G1-2) cancers and between different degrees of muscle invasivity; ensemble model accuracies were ≥80%. Relevant metabolites, selected using the partial least square discriminant analysis (PLS-DA) algorithm, were included in a metabolite-set enrichment analysis, showing perturbations primarily associated with cell glucose metabolism. The metabolomic approach may be useful as a non-invasive screening tool for bladder cancer. Furthermore, metabolic pathway analysis can increase understanding of cancer pathophysiology. Studies conducted on larger cohorts, and including blind trials, are needed to validate results.

Las primeras indagaciones en la estructura y composición de la ictiofauna en los ríos de Cuba la realizó el naturalista cubano Felipe Poey. Numerosas han sido las investigaciones realizadas en este campo, principalmente en la región occidental y central de Cuba. Este trabajo se propuso determinar la distribución y similitud de los grupos de especies ícticas dulceacuícolas de las diferentes localidades del municipio Gibara. Se determinó el número de especies por cada localidad, se calculó la similitud a través del índice de Bray-Curtis y el rango de distancia de disimilitud entre las localidades mediante el escalado multidimensional no métrico, el cual permite construir un mapa de ordenamiento del número específico de dimensiones. Se registraron 30 especies, de ellas dos marinas y dos nuevos morfos, que probablemente constituyan especies nuevas. Se agruparon en nueve órdenes, 14 familias y 25 géneros. Las localidades con mayor número de especies fueron las que presentaron una amplia red fluvial tales como, Uñas con 22, Floro Pérez 20, Velasco Uno 19, Cañada de Melones 18, Bocas 17 y Velasco Dos 16. El 30% de las especies son endémicas, con un mayor número en las localidades Velasco Uno, Uña, y Velasco Dos. Las especies exóticas estuvieron presentes en un 18.75%, distribuidas en mayor cantidad en Uñas y Cañada de Melones con seis especies cada una. Las especies autóctonas representaron el 50% del total especies ubicadas principalmente en Floro Pérez, Uña y Velasco Uno. Los resultados del estudio de asociaciones mostraron dos grandes grupos a un 46% de similitud y se obtuvo un nivel de estrés de 0.01 lo que demuestra un buen ajuste del orden espacial y proporción de la distancia ecológica.